Preparation of rifampin

A technology of rifampicin and rifamycin, applied in organic chemistry, antibacterial drugs, etc., can solve problems such as high cost and unsatisfactory product quality

Active Publication Date: 2011-01-26
薛荔 +1
View PDF3 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0007] The purpose of the present invention is to provide a preparation method of high-quality rifampicin, which solves the problems of unsatisfactory product quality and high cost in traditional preparation methods. Compared with the existing preparation process, it can significantly improve product purity and reduce production costs. It can control the total amount of miscellaneous peaks to less than 1.5%, so that the total consumption of raw materials can be reduced by two-thirds, and the consumption of precious raw material 1-methyl-4-aminopiperazine can be reduced by more than one-half, and the pollution of strong acids and alkalis to the environment can also be eradicated

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Examples

Experimental program
Comparison scheme
Effect test

preparation example Construction

[0029] The operation steps of the first batch and subsequent batch preparation methods of high-quality rifampicin of the present invention are as follows:

[0030] Step one salt reaction

[0031] In the first batch of production, the rifamycin SV is oxidized to produce S and then extracted with BA to obtain the S-BA feed liquid as the starting material, concentrated to 100-140 thousand u / ml, from which 50 million units are taken S-BA concentrated feed solution of S, drop 100-250ml of 6% sodium bicarbonate aqueous solution, control 30~50℃ to react for 3~6h to generate S sodium salt, cool to no higher than 10℃, crystallize and filter to obtain the product, and recover the mother liquor To be recycled. When continuing batch production, you can also directly take the S-BA concentrated feed solution equivalent to 50 million units of rifamycin S and the previous batch of recovered mother liquor, repeat the above-mentioned salt formation reaction, and regularly neutralize the recovered m...

Embodiment 1

[0039] The rifamycin SV is oxidized to produce S, and then extracted with BA to obtain the S-BA feed liquid as the starting material, which is concentrated to 100,000 to 140,000 u / ml, and 50 million units of S are taken from the concentrated feed liquid Add 150ml of 6% sodium bicarbonate aqueous solution at 45℃ and maintain the reaction for 5h. After the reaction, the temperature will be cooled to 10℃ and the crystal will be filtered by suction. The filter cake will be washed with purified water and then drained. Controlled at 60℃ and dried under reduced pressure to obtain S The sodium salt is about 45 grams, and the mother liquor is recovered for recycling. Sodium salt was added to 90ml DMF containing 3.8ml of acetic acid, stirred at 50°C for 30 minutes to be freed into S, and then 14.4ml of dihydroxy cyclization reaction was added dropwise for 1 hour to obtain oxazine. DMF is recovered by molecular distillation. After recovery, an appropriate amount of ethanol is added to dis...

Embodiment 2

[0041] The rifamycin SV is oxidized to produce S and then extracted with BA to obtain the S-BA feed liquid as the starting material, and then concentrate to 100-140 thousand u / ml, and take 50 million units of S from the concentrated feed liquid Add 150ml of 6% sodium bicarbonate aqueous solution at 45℃ and maintain the reaction for 5h. After the reaction, the temperature will be cooled to 10℃ and the crystallization will be filtered by suction. The filter cake will be washed with purified water and drained. Controlled at 60℃ and dried under reduced pressure to obtain S The sodium salt is about 45 grams, and the mother liquor is recovered for recycling. Sodium salt was added to 90ml DMF containing 3.8ml of acetic acid, stirred at 50°C for 30 minutes to be freed into S, and then 14.4ml of dihydroxy cyclization reaction was added dropwise for 1 hour to obtain oxazine. DMF is recovered by molecular distillation. After recovery, an appropriate amount of ethanol is added to dissolve ...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

PUM

No PUM Login to View More

Abstract

The invention discloses a preparation method of high-quality rifampicin, solving the problem that the traditional preparation method has the defects such as unfavorable product quality and high cost; the preparation method comprises the operational steps: S-BA liquid is salified by alkalescence sodium bicarbonate during a salification reaction; S is separated out by acetate acid before a cyclization reaction; then, dihydroxy is added for a reaction to obtain oxazine; after the reaction is finished, DMF is recovered by a molecular distillation method and then dissolved by other hydrophilic solvents; oxazine is separated out by an elutriation method; after a hydrolysis reaction and a condensation reaction are finished, an azeotropic distillation method is adopted to recover un-reacted side chains; pH is adjusted and temperature is lowered so that crystals are separated to obtain the crude products of rifampicin; and then the crude products are refined to obtain the high-quality rifampicin. Compared with the existing preparation technique, the preparation method significantly improves the product purity, reduces the production cost, controls the overall quantity of impurities to be lower than 1.5 percent, reduces two thirds of the general consumption of raw materials and more than a half of the usage of 1-methyl-4-aminopyrazine which is a valuable raw material, and eliminates theenvironmental pollution caused by strong acid and alkali.

Description

Technical field [0001] The invention relates to an anti-tuberculosis drug production process, in particular to a preparation method of using rifamycin SV as a raw material to produce high-quality, low-cost, and environmentally friendly high-quality rifampicin. Background technique [0002] Rifampicin is a semi-synthetic antibiotic of the rifamycin class and is an important anti-tuberculosis drug. According to reports, rifampicin is also a broad-spectrum antibiotic, except for its high activity against tuberculosis; against Staphylococcus aureus, non-enterococcal streptococci and Listeria monocytogenes Bacteria are also highly active; it is also the most effective treatment for non-tuberculosis including tuberculous meningitis. [0003] The preparation method of rifampicin generally uses rifamycin SV fermentation filtrate at home and abroad, and oxidizes it to rifamycin S with a strong oxidizing agent such as ferric chloride. A large amount of concentrated hydrochloric acid is used...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

Application Information

Patent Timeline
no application Login to View More
Patent Type & AuthorityPatents(China)
IPC IPC(8): C07D498/08A61P31/06
Inventor薛守礼杜明山郑洪权董喜武邱桂侠王亚钧朱焱关甦薛荔
Owner薛荔